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Nuclear localization of YAP is associated with tumor progression in cutaneous melanoma Lab. Invest. (IF 5.0) Pub Date : 2024-03-14 Hyang Joo Ryu, Chayeon Kim, Hyenguk Jang, Sun Il Kim, Sang Joon Shin, Kee Yang Chung, Carlos Torres-Cabala, Sang Kyum Kim
Yes-associated protein (YAP), an effector molecule of the Hippo signaling pathway, is expressed at high levels in cutaneous melanoma. However, the role of YAP in melanoma progression according to cellular localization is poorly understood. Tissues from 140 patients with invasive melanoma were evaluated by immunohistochemistry. Flow cytometry, Western blotting, viability assays, wound healing assays
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Sex-specific stone-forming phenotype in mice during hypercalciuria/urine alkalinization Lab. Invest. (IF 5.0) Pub Date : 2024-03-05 Eugenia Awuah Boadi, Samuel Shin, Bok-Eum Choi, Khanh Ly, Christopher B. Raub, Bidhan C. Bandyopadhyay
Gender disparities in kidney stone formation are well-known. Women generally have slightly acidic blood and higher urine pH when compared with men, which makes them more vulnerable to calcium stone formation, yet the mechanism is still unclear. We aimed to examine the role of sex in stone formation during hypercalciuria and urine alkalinization through acetazolamide (Acz) and calcium gluconate (CaG)
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SIRT1: an Intermediator of Key Pathways Regulating Pulmonary Diseases Lab. Invest. (IF 5.0) Pub Date : 2024-03-05 Yi-Zhu Jiang, Xin-Ran Huang, Jing Chang, Yong Zhou, Xiao-Ting Huang
Silent information regulator type-1 (SIRT1), a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, is a member of the sirtuins family and has unique protein deacetylase activity. SIRT1 participates in physiological as well as pathophysiological processes by targeting a wide range of protein substrates and signalings. In this review, we describe the latest progress of SIRT1 in pulmonary diseases
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Expression of SOX4 Significantly Predicts the Risk of Lymph Node Metastasis for Patients With Early-Stage Esophageal Squamous Cell Carcinoma Lab. Invest. (IF 5.0) Pub Date : 2024-03-01 Yifei Zhang, Yanbo Liu, Linfeng Wu, Tianyin Chen, Heng Jiao, Yuanyuan Ruan, Pinghong Zhou, Yiqun Zhang
Esophageal squamous cell carcinoma stands as a notably aggressive malignancy within the digestive system. In cases of early esophageal cancer without lymph node metastasis, endoscopic surgical resection offers a viable alternative, often resulting in improved patient quality of life. However, the paucity of methods to preoperatively ascertain lymph node involvement complicates surgical planning. SOX4
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Advancing Artificial Intelligence Integration Into the Pathology Workflow: Exploring Opportunities in Gastrointestinal Tract Biopsies Lab. Invest. (IF 5.0) Pub Date : 2024-02-29 Fazilet Yilmaz, Arlen Brickman, Fedaa Najdawi, Evgeny Yakirevich, Robert Egger, Murray B. Resnick
This review aims to present a comprehensive overview of the current landscape of artificial intelligence (AI) applications in the analysis of tubular gastrointestinal biopsies. These publications cover a spectrum of conditions, ranging from inflammatory ailments to malignancies. Moving beyond the conventional diagnosis based on hematoxylin and eosin–stained whole-slide images, the review explores additional
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Pathogenic Roles for RNASET2 in Clear Cell Renal Cell Carcinoma Lab. Invest. (IF 5.0) Pub Date : 2024-02-29 Taylor Peak, Yijun Tian, Aman Patel, Tim Shaw, Alyssa Obermayer, Jose Laborde, Youngchul Kim, Joseph Johnson, Paul Stewart, Bin Fang, Jamie K. Teer, John Koomen, Anders Berglund, Doug Marchion, Natasha Francis, Paola Ramos Echevarria, Jasreman Dhillon, Noel Clark, Andrew Chang, Wade Sexton, Logan Zemp, Jad Chahoud, Liang Wang, Brandon Manley
A specific splicing isoform of is associated with worse oncologic outcomes in clear cell renal cell carcinoma (ccRCC). However, the interplay between wild-type RNASET2 and its splice variant and how this might contribute to the pathogenesis of ccRCC remains poorly understood. We sought to better understand the relationship of RNASET2 in the pathogenesis of ccRCC and the interplay with a pathogenic
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Proteomic Profiles of Human Arterioles Isolated From Fresh Adipose Tissue or Following Overnight Storage Lab. Invest. (IF 5.0) Pub Date : 2024-02-24 Rajan Pandey, Michelle L. Roberts, Jingli Wang, Michaela Pereckas, David Jensen, Andrew S. Greene, Michael E. Widlansky, Mingyu Liang
Arterioles are key determinants of the total peripheral vascular resistance, which, in turn, is a key determinant of arterial blood pressure. However, the amount of protein available from one isolated human arteriole may be less than 5 μg, making proteomic analysis challenging. In addition, obtaining human arterioles requires manual dissection of unfrozen clinical specimens. This limits its feasibility
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Bile Acid Receptor Agonist Reverses Transforming Growth Factor-β1–Mediated Fibrogenesis in Human Induced Pluripotent Stem Cells–Derived Kidney Organoids Lab. Invest. (IF 5.0) Pub Date : 2024-01-22 Xiaoping Yang, Marco Delsante, Parnaz Daneshpajouhnejad, Paride Fenaroli, Kira Perzel Mandell, Xiaoxin Wang, Shogo Takahashi, Marc K. Halushka, Jeffrey B. Kopp, Moshe Levi, Avi Z. Rosenberg
Chronic kidney disease progresses through the replacement of functional tissue compartments with fibrosis, a maladaptive repair process. Shifting kidney repair toward a physiologically intact architecture, rather than fibrosis, is key to blocking chronic kidney disease progression. Much research into the mechanisms of fibrosis is performed in rodent models with less attention to the human genetic context
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HSPB6 Deficiency Promotes the Development of Aortic Dissection and Rupture Lab. Invest. (IF 5.0) Pub Date : 2024-01-17 Shiqi Gao, Kai Zhang, Chenyu Zhou, Jian Song, Yuanrui Gu, Fangfang Cao, Ji Wang, Enzehua Xie, Cuntao Yu, Juntao Qiu
To better understand the pathogenesis of acute type A aortic dissection, high-sensitivity liquid chromatography–tandem mass spectrometry/mass spectrometry (LC-MS/MS)-based proteomics and phosphoproteomics approaches were used to identify differential proteins. Heat shock protein family B (small) member 6 (HSPB6) in aortic dissection was significantly reduced in human and mouse aortic dissection samples
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Nuclear Nicotinamide Adenine Dinucleotide Deficiency by Nmnat1 Deletion Impaired Hepatic Insulin Signaling, Mitochondrial Function, and Hepatokine Expression in Mice Fed a High-Fat Diet Lab. Invest. (IF 5.0) Pub Date : 2024-01-16 Haibo Dong, Wei Guo, Ruichao Yue, Xinguo Sun, Zhanxiang Zhou
Metabolic syndrome (MetS) is a worldwide challenge that is closely associated with obesity, nonalcoholic liver disease, insulin resistance, and type 2 diabetes. Boosting nicotinamide adenine dinucleotide (NAD) presents great potential in preventing MetS. However, the function of nuclear NAD in the development of MetS remains poorly understood. In this study, hepatocyte-specific Nmnat1 knockout mice
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Tumor-Infiltrating Mast Cells in Angiosarcoma Correlate With Immuno-Oncology Pathways and Adverse Clinical Outcomes Lab. Invest. (IF 5.0) Pub Date : 2024-01-11 Sarah Beishan Tai, Elizabeth Chun Yong Lee, Boon Yee Lim, Bavani Kannan, Jing Yi Lee, Zexi Guo, Tun Kiat Ko, Cedric Chuan-Young Ng, Bin Tean Teh, Jason Yongsheng Chan
Recent studies have described several molecular subtypes and deregulation of immuno-oncologic signaling pathways in angiosarcoma. Interestingly, mast cells were enriched in subsets of angiosarcoma, although their significance remains unknown. In this study, we aim to verify this observation using immunohistochemistry (H scores) and NanoString transcriptomic profiling and explore the association between
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Ultrastructural Examination of Glomerular Fibrillary Deposits in Diabetic Nephropathy Lab. Invest. (IF 5.0) Pub Date : 2023-12-30 Sophie I. Nagelkerken, Peter H. Neeskens, Joris I. Rotmans, Volker Nickeleit, Jan A. Bruijn, Ingeborg M. Bajema
Glomerular fibrillary deposits have occasionally been reported in diabetic nephropathy, but no large-scale, ultrastructural evaluation of these deposits has been reported so far. Here, we report our study of glomerular non-Congophilic, DnaJ homolog subfamily B member 9 negative fibrillary deposits in diabetic nephropathy as characterized by transmission electron microscopy. Clinical data from 55 patients
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Union With Recursive Feature Elimination: A Feature Selection Framework to Improve the Classification Performance of Multicategory Causes of Death in Colorectal Cancer Lab. Invest. (IF 5.0) Pub Date : 2023-12-28 Fei Deng, Lin Zhao, Ning Yu, Yuxiang Lin, Lanjing Zhang
Despite the use of machine learning tools, it is challenging to properly model cause-specific deaths in colorectal cancer (CRC) patients and choose appropriate treatments. Here, we propose an interesting feature selection framework, namely union with recursive feature elimination (U-RFE), to select the union feature sets that are crucial in CRC progression-specific mortality using The Cancer Genome
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COX-2/sEH-Mediated Macrophage Activation Is a Target for Pulmonary Protection in Mouse Models of Chronic Obstructive Pulmonary Disease Lab. Invest. (IF 5.0) Pub Date : 2023-12-27 Jia-Xi Duan, Xin-Xin Guan, Wei Cheng, Ding-Ding Deng, Ping Chen, Cong Liu, Yong Zhou, Bruce D. Hammock, Hui-Hui Yang
Effective inhibition of macrophage activation is critical for resolving inflammation and restoring pulmonary function in patients with chronic obstructive pulmonary disease (COPD). In this study, we identified the dual-enhanced cyclooxygenase-2 (COX-2)/soluble epoxide hydrolase (sEH) as a novel regulator of macrophage activation in COPD. Both COX-2 and sEH were found to be increased in patients and
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In ER-Positive, HER2-Negative Breast Cancers, HER2 mRNA Levels Correlate Better with Clinicopathologic Features and Oncotype DX Recurrence Score than HER2 Immunohistochemistry Lab. Invest. (IF 5.0) Pub Date : 2023-12-20 Haley Tyburski, Cansu Karakas, Brian S. Finkelman, Bradley M. Turner, Huina Zhang, David G. Hicks MD
With the approval of trastuzumab deruxtecan for treating advanced human epidermal growth factor receptor-2 (HER2) low breast cancer (BC), it has become increasingly important to develop more accurate and reliable methods to identify HER2-low BC. In addition, HER2 immunohistochemistry (IHC) has limitations for quantification of HER2. We explored the relationship between HER2 IHC and mRNA levels and
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The Prognostic Value of CD39 as a Marker of Tumor-Specific T Cells in Triple-Negative Breast Cancer in Asian Women Lab. Invest. (IF 5.0) Pub Date : 2023-12-14 Jia Meng, Jing Ying Tira Tan, Craig Ryan Joseph, Jiangfeng Ye, Jeffrey Chun Tatt Lim, Denise Goh, Yuezhen Xue, Xinru Lim, Valerie Cui Yun Koh, Felicia Wee, Timothy Kwang Yong Tay, Jaason Yongsheng Chan, Cedric Chuan Young Ng, Jabed Iqbal, Mai Chan Lau, Hsuen Elaine Lim, Han Chong Toh, Bin Tean Teh, Rebecca Alexandra Dent, Puay Hoon Tan, Joe Poh Sheng Yeong
Triple-negative breast cancer (TNBC) has a poor prognosis with limited therapeutic options available for affected patients. Efforts are ongoing to identify surrogate markers for tumor-specific CD8 T cells that can predict the response to immune checkpoint inhibitor (ICI) therapies, such as programmed cell death protein 1 or programmed cell death ligand-1 blockade. We have previously identified tumor-specific
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Development and Validation of a Multiclass Model Defining Molecular Archetypes of Kidney Transplant Rejection: A Large Cohort Study of the Banff Human Organ Transplant Gene Expression Panel Lab. Invest. (IF 5.0) Pub Date : 2023-12-12 Hao Zhang, Randy S. Haun, Francois Collin, Clarissa Cassol, Johnathan O.H. Napier, Jon Wilson, Samar Hassen, Kerime Ararat, Christie Boils, Nidia Messias, Tiffany N. Caza, L. Nicholas Cossey, Shree Sharma, Josephine M. Ambruzs, Nikhil Agrawal, Grigoriy Shekhtman, Wenlan Tian, Titte Srinivas, Kunbin Qu, Robert N. Woodward, Christopher P. Larsen, Steven Stone, Shana M. Coley
Gene expression profiling from formalin-fixed paraffin-embedded (FFPE) renal allograft biopsies is a promising approach for feasibly providing a molecular diagnosis of rejection. However, large-scale studies evaluating the performance of models using NanoString platform data to define molecular archetypes of rejection are lacking. We tested a diverse retrospective cohort of over 1400 FFPE biopsy specimens
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The Detection of Neoplastic Cells Using Objective Cytomorphologic Parameters in Malignant Lymphoma Lab. Invest. (IF 5.0) Pub Date : 2023-12-12 Miharu Nagaishi, Hiroaki Miyoshi, Mauricio Kugler, Kensaku Sato, Kei Kohno, Mai Takeuchi, Kyohei Yamada, Takuya Furuta, Noriaki Hashimoto, Ichiro Takeuchi, Hidekata Hontani, Koichi Ohshima
Pathologic evaluation is the most crucial method for diagnosing malignant lymphomas. However, there are no established diagnostic criteria for evaluating pathologic morphology. We manually circled cell nuclei in the lesions of 10 patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, and reactive lymphadenitis. Seventeen parameters related to nuclear shape, color, and other characteristics
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FFPE Proteomics of Malignant Mesothelioma and New Candidate Biomarkers Thioredoxin and Superoxide Dismutase 2 for Immunohistochemistry. Lab. Invest. (IF 5.0) Pub Date : 2023-11-25 Takuya Hiratsuka,Akihiko Yoshizawa,Tatsuya Endo,Takushi Yamamoto,Shinya Toyokuni,Tatsuaki Tsuruyama
The pathogenesis of malignant mesothelioma (MM) has been extensively investigated, focusing on stress derived from reactive oxygen species (ROS). We aimed to identify diagnostic biomarkers of MM by analyzing proteins in formalin-fixed paraffin-embedded specimens (FFPE) using liquid chromatography-mass spectrometry. We extracted proteins from FFPE sections of MM tissues (n = 6) and compared their profiles
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Recent advances in enterovirus A71 infection and antiviral agents. Lab. Invest. (IF 5.0) Pub Date : 2023-11-24 Yanhong Wei,Huihui Liu,Da Hu,Qun He,Chenguang Yao,Hanluo Li,Kanghong Hu,Jun Wang
Enterovirus A71 (EV-A71) is one of the major causative agents of hand-foot-and-mouth disease (HFMD) that majorly affects children. Most of the time, HFMD is a mild disease but can progress to severe complications such as meningitis, brain stem encephalitis, acute flaccid paralysis (AFP) and even death. HFMD caused by EV-A71 has emerged as an acutely infectious disease of highly pathogenic potential
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An innovative and accurate next-generation sequencing-based microsatellite instability detection method for colorectal and endometrial tumors. Lab. Invest. (IF 5.0) Pub Date : 2023-11-24 Camille Evrard,Ulrich Cortes,Birama Ndiaye,Justine Bonnemort,Marine Martel,Roxanne Aguillon,David Tougeron,Lucie Karayan-Tapon
The detection of microsatellite instability (MSI) and mismatch repair deficiency (dMMR) has become mandatory for most tumors in recent years, owing to the development of immune checkpoint inhibitors (ICIs) as a highly effective therapy for dMMR/MSI tumors. The timely and efficient detection of MSI is valuable, and new methods are increasingly being developed. To date, MMR assessment has been performed
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Detection of large-droplet macrovesicular steatosis in donor Livers based on segment-anything model. Lab. Invest. (IF 5.0) Pub Date : 2023-11-15 Haiming Tang,Jingjing Jiao,Jian Denny Lin,Xuchen Zhang,Nanfei Sun
Liver transplantation is an effective treatment for end-stage liver disease, acute liver failure, and primary hepatic malignancy. However, the limited availability of donor organs remains a challenge. Severe large-droplet fat (LDF) macrovesicular steatosis, characterized by cytoplasmic replacement with large vacuoles, can lead to liver transplant complications. Artificial intelligence (AI) models,
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A Novel Mathematical Approach for Analysis of Integrated Cell-Patient Data Uncovers a 6-Gene Signature Linked to Endocrine Therapy Resistance. Lab. Invest. (IF 5.0) Pub Date : 2023-11-10 Martin Parga-Pazos,Nicole Cusimano,Miriam Rábano,Elena Akhmatskaya,Maria dM Vivanco
A significant number of breast cancers develop resistance to hormone therapy. This progression, while posing a major clinical challenge, is difficult to predict. Despite important contributions made by cell models and clinical studies to tackle this problem, both present limitations when taken individually. Experiments with cell models are highly reproducible but do not reflect the indubitable heterogenous
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Omic Studies on In Vitro Cystinosis Model: siRNA-Mediated CTNS Gene Silencing in HK-2 Cells. Lab. Invest. (IF 5.0) Pub Date : 2023-11-09 İpek Baysal,Samiye Yabanoglu-Ciftci,Emirhan Nemutlu,Cemil Can Eylem,Elif Damla Gök-Topak,Kezban Ulubayram,Sedef Kır,Bora Gulhan,Gülberk Uçar,Fatih Ozaltin,Rezan Topaloglu
Cystinosis is an autosomal recessive disease caused by mutations in the CTNS gene encoding a protein called cystinosine, which is a lysosomal cystine transporter. Disease-causing mutations lead to accumulation of cystine crystals in the lysosomes, thereby causing dysfunction of vital organs. Determination of the increased leukocyte cystine level is one of the most used methods for diagnosis. However
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Characterization of immune cell populations of cutaneous neurofibromas in neurofibromatosis 1. Lab. Invest. (IF 5.0) Pub Date : 2023-11-08 Roope A Kallionpää,Sirkku Peltonen,Kim My Le,Eija Martikkala,Mira Jääskeläinen,Elnaz Fazeli,Pilvi Riihilä,Pekka Haapaniemi,Anne Rokka,Marko Salmi,Ilmo Leivo,Juha Peltonen
Cutaneous neurofibromas (cNFs) are characteristic of neurofibromatosis 1 (NF1), yet their immune microenvironment is incompletely known. A total of 61 cNFs from ten patients with NF1 were immunolabeled for different types of T cells and macrophages, and the cell densities were correlated with clinical characteristics. Eight cNFs and their overlying skin were analyzed for T cell receptor (TCR) CDR domain
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Global ring study to investigate the comparability of total assay performance of commercial claudin 18 antibodies for evaluation in gastric cancer. Lab. Invest. (IF 5.0) Pub Date : 2023-11-08 Bharat Jasani,Philippe Taniere,Hans-Ulrich Schildhaus,Kevin Blighe,Suzanne Parry,Dawn Wilkinson,Neil Atkey,Scott Clare-Antony,Clare McCabe,Christine Quinn,,Andrew Dodson
Claudin 18.2 (CLDN18.2), the dominant isoform of CLDN18 in gastric tissue, is a highly specific tight junction protein of the gastric mucosa with variably retained expression in gastric and gastroesophageal junction cancer. CLDN18.2-targeted treatment with zolbetuximab in combination with chemotherapy has recently been assessed in two phase III studies of patients with HER2-negative, locally advanced
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Osteosarcomas With Few Chromosomal Alterations or Adult Onset Are Genetically Heterogeneous. Lab. Invest. (IF 5.0) Pub Date : 2023-11-04 Valeria Difilippo,Karim H Saba,Emelie Styring,Linda Magnusson,Jenny Nilsson,Michaela Nathrath,Daniel Baumhoer,Karolin H Nord
Osteosarcoma is the most common primary bone malignancy, often detected in children and adolescents and commonly associated with TP53 alterations along with a high number of chromosomal rearrangements. However, osteosarcoma can affect patients of any age, and some tumors display less genetic complexity. Besides TP53 variants, data on key driving mutations are lacking for many osteosarcomas, particularly
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A High-Throughput PIXUL-Matrix-Based Toolbox to Profile Frozen and Formalin-Fixed Paraffin-Embedded Tissues Multiomes. Lab. Invest. (IF 5.0) Pub Date : 2023-11-03 Daniel Mar,Ilona M Babenko,Ran Zhang,William Stafford Noble,Oleg Denisenko,Tomas Vaisar,Karol Bomsztyk
Large-scale high-dimensional multiomics studies are essential to unravel molecular complexity in health and disease. We developed an integrated system for tissue sampling (CryoGrid), analytes preparation (PIXUL), and downstream multiomic analysis in a 96-well plate format (Matrix), MultiomicsTracks96, which we used to interrogate matched frozen and formalin-fixed paraffin-embedded (FFPE) mouse organs
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A Multicenter Study Validates the WHO 2022 Classification for Conjunctival Melanocytic Intraepithelial Lesions With Clinical and Prognostic Relevance. Lab. Invest. (IF 5.0) Pub Date : 2023-11-03 Hardeep Singh Mudhar,Yamini Krishna,Simon Cross,Claudia Auw-Haedrich,Raymond Barnhill,Svetlana Cherepanoff,Ralph Eagle,James Farmer,Robert Folberg,Hans Grossniklaus,Martina C Herwig-Carl,Martin Hyrcza,Sandra Lassalle,Karin U Loeffler,Alexandre Moulin,Tatyana Milman,Robert M Verdijk,Steffen Heegaard,Sarah E Coupland
Several nomenclature and grading systems have been proposed for conjunctival melanocytic intraepithelial lesions (C-MIL). The fourth "WHO Classification of Eye Tumors" (WHO-EYE04) proposed a C-MIL classification, capturing the progression of noninvasive neoplastic melanocytes from low- to high-grade lesions, onto melanoma in situ (MIS), and then to invasive melanoma. This proposal was revised to the
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Integration of RNA Sequencing, Whole Exome Sequencing, and Flow Cytometry Into Routine Diagnostic Workup of Pediatric Lymphomas. Lab. Invest. (IF 5.0) Pub Date : 2023-10-26 Marijn A Scheijde-Vermeulen,Lennart A Kester,Liset Westera,Bastiaan B J Tops,Friederike A G Meyer-Wentrup
The study was conducted to assess the feasibility of integrating state-of-the-art sequencing techniques and flow cytometry into diagnostic workup of pediatric lymphoma. RNA sequencing (RNAseq), whole exome sequencing, and flow cytometry were implemented into routine diagnostic workup of pediatric biopsies with lymphoma in the differential diagnosis. Within 1 year, biopsies from 110 children (122 specimens)
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Quantitative Histomorphometric Features of Prostate Cancer Predict Patients Who Biochemically Recur Following Prostatectomy. Lab. Invest. (IF 5.0) Pub Date : 2023-10-26 Savannah R Duenweg,Michael Brehler,Allison K Lowman,Samuel A Bobholz,Fitzgerald Kyereme,Aleksandra Winiarz,Biprojit Nath,Kenneth A Iczkowski,Kenneth M Jacobsohn,Peter S LaViolette
Prostate cancer is the most commonly diagnosed cancer in men, accounting for 27% of the new male cancer diagnoses in 2022. If organ-confined, removal of the prostate through radical prostatectomy is considered curative; however, distant metastases may occur, resulting in a poor patient prognosis. This study sought to determine whether quantitative pathomic features of prostate cancer differ in patients
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Targeting SIRT4/TET2 signaling alleviates human keratinocyte senescence by reducing 5-hmC loss. Lab. Invest. (IF 5.0) Pub Date : 2023-10-26 Yi Yi,Yuchang Wang,Yiping Wu,Yukun Liu
Skin aging is characterized by wrinkle formation and increased frailty and laxity, leading to the risk of age-related skin disease. The keratinocyte is an important component of the epidermis in skin structure, and keratinocyte senescence has been identified as a pivotal factor in skin aging development. Because epigenetic pathways play a vital role in the regulation of skin aging, we evaluated human
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Melatonin Alleviates Acute Respiratory Distress Syndrome by Inhibiting Alveolar Macrophage NLRP3 Inflammasomes Through the ROS/HIF-1α/GLUT1 Pathway. Lab. Invest. (IF 5.0) Pub Date : 2023-10-21 Li Zheng,Wenyu Zhou,Yutong Wu,Wenting Xu,Song Hu,Yiguo Zhang,Huan Xu,Huimin Deng,Yuanli Chen,Lingmin Wu,Juan Wei,Di Feng,Mansi Wang,Huanping Zhou,Quanfu Li,Lina Zhu,Hao Yang,Xin Lv
Sepsis-induced acute respiratory distress syndrome (ARDS) is a devastating clinically severe respiratory disorder, and no effective therapy is available. Melatonin (MEL), an endogenous neurohormone, has shown great promise in alleviating sepsis-induced ARDS, but the underlying molecular mechanism remains unclear. Using a lipopolysaccharide (LPS)-treated mouse alveolar macrophage cell line (MH-S) model
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Visual Assessment of 2-Dimensional Levels Within 3-Dimensional Pathology Data Sets of Prostate Needle Biopsies Reveals Substantial Spatial Heterogeneity. Lab. Invest. (IF 5.0) Pub Date : 2023-10-18 Can Koyuncu,Andrew Janowczyk,Xavier Farre,Tilak Pathak,Tuomas Mirtti,Pedro L Fernandez,Laura Pons,Nicholas P Reder,Robert Serafin,Sarah S L Chow,Vidya S Viswanathan,Adam K Glaser,Lawrence D True,Jonathan T C Liu,Anant Madabhushi
Prostate cancer prognostication largely relies on visual assessment of a few thinly sectioned biopsy specimens under a microscope to assign a Gleason grade group (GG). Unfortunately, the assigned GG is not always associated with a patient's outcome in part because of the limited sampling of spatially heterogeneous tumors achieved by 2-dimensional histopathology. In this study, open-top light-sheet
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TC2N Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma by Targeting the Wnt/β-Catenin Signaling Pathway. Lab. Invest. (IF 5.0) Pub Date : 2023-10-13 Yi-Xia Lou,Jing Gu,Lei Zhu,Sheng-Qi Sun,Xiang-Lin Hao,Jian-Ping Chen,Fei Han,Dan-Dan Wang,Xiao Jiang,Jin-Yi Liu
Hepatocellular carcinoma (HCC), one of the most prevalent types of cancer worldwide, has an exceedingly poor prognosis. Tandem C2 domain nuclear protein (TC2N) has been implicated in tumorigenesis and serves as an oncogene or tumor suppressor in different types of cancer. Here, we explore the possible regulatory activities and molecular mechanisms of TC2N in HCC progression. However, TC2N expression
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Real-World Implementation of Digital Pathology: Results From an Intercontinental Survey. Lab. Invest. (IF 5.0) Pub Date : 2023-10-13 Daniel Gomes Pinto,Andrey Bychkov,Naoko Tsuyama,Junya Fukuoka,Catarina Eloy
The past 70 years have been characterized by rapid advancements in computer technology, and the health care system has not been immune to this trend. However, anatomical pathology has remained largely an analog discipline. In recent years, this has been changing with the growing adoption of digital pathology, partly driven by the potential of computer-aided diagnosis. As part of an international collaboration
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Spatial Proximity and Relative Distribution of Tumor-Infiltrating Lymphocytes and Macrophages Predict Survival in Melanoma. Lab. Invest. (IF 5.0) Pub Date : 2023-10-13 Francesco De Logu,Filippo Ugolini,Luigi Francesco Iannone,Sara Simi,Vincenza Maio,Vincenzo de Giorgi,Anna Maria di Giacomo,Clelia Miracco,Antonio Cossu,Giuseppe Palmieri,Mario Mandalà,Daniela Massi
Tumor microenvironment plays a crucial role in primary cutaneous melanoma (CM) progression. Although the role of tumor-infiltrating lymphocyte (TIL) density has been known for a long time, its spatial distribution and impact with or without tumor-associated macrophages (TAMs) remain controversial. Herein, we investigated spatial proximity between tumor cells and immune cells in 113 primary CM and its
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ZMIZ1 Upregulation of TET3-Mediated Hydroxymethylation Induces M2 Polarization of Kupffer Cells in Hepatocellular Carcinogenesis by Mediating Notch1/c-Myc Signaling. Lab. Invest. (IF 5.0) Pub Date : 2023-10-13 Jia Liu,Tingting Sun,Linan Yin
Hydroxymethylation of DNA, mediated by the ten-eleven translocation (TET) family of methylcytosine dioxygenases, represents a crucial epigenetic modification that manipulates gene expression in numerous biological processes. This study focuses on the effect of TET3 on the polarization of Kupffer cells (KCs) and its connection to the development of hepatocellular carcinoma (HCC). TET3 was found to be
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Comparing Accuracy of Helicobacter pylori Identification Using Traditional Hematoxylin and Eosin-Stained Glass Slides With Digital Whole Slide Imaging. Lab. Invest. (IF 5.0) Pub Date : 2023-10-13 Wei Chen,Jennifer Ziebell,Vidya Arole,Bryce Parkinson,Lianbo Yu,Harrison Dai,Wendy L Frankel,Martha Yearsley,Ashwini Esnakula,Shaoli Sun,Denise Gamble,Jennifer Vazzano,Manisha Mishra,Lynn Schoenfield,Jeffrey Kneile,Sarah Reuss,Melinda Schumacher,Swati Satturwar,Zaibo Li,Anil Parwani,Giovanni Lujan
With advancements in the field of digital pathology, there has been a growing need to compare the diagnostic abilities of pathologists using digitized whole slide images against those when using traditional hematoxylin and eosin (H&E)-stained glass slides for primary diagnosis. One of the most common specimens received in pathology practices is an endoscopic gastric biopsy with a request to rule out
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Expression of IDO1 in Tumor Microenvironment Significantly Predicts the Risk of Recurrence/Distant Metastasis for Patients With Esophageal Squamous Cell Carcinoma. Lab. Invest. (IF 5.0) Pub Date : 2023-10-13 Cen Qiu,Qingyuan Lin,Saiyan Ji,Chenjie Han,Qingyuan Yang
In this study, we aimed to explore immune markers predicting locoregional recurrence/distant metastasis (R/M) for patients with esophageal squamous cell carcinoma (ESCC) post-surgical intervention by using a novel high-throughput spatial tool to quantify multiple immune proteins expressed in ESCC and lymphocytes in tumor microenvironment (TME-L). First, formalin-fixed paraffin-embedded tissues from
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Evaluation of A Computer-Aided Detection Software for Prostate Cancer Prediction: Excellent Diagnostic Accuracy Independent of Preanalytical Factors. Lab. Invest. (IF 5.0) Pub Date : 2023-10-07 Jennifer Vazzano,Dorota Johansson,Kun Hu,Kristian Eurén,Stefan Elfwing,Anil Parwani,Ming Zhou
Prostate cancer (PCa) is the most common noncutaneous cancer in men in the Western world. In addition to accurate diagnosis, Gleason grading and tumor volume estimates are critical for patient management. Computer-aided detection (CADe) software can be used to facilitate the diagnosis and improve the diagnostic accuracy and reporting consistency. However, preanalytical factors such as fixation and
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Revolutionizing Digital Pathology With the Power of Generative Artificial Intelligence and Foundation Models. Lab. Invest. (IF 5.0) Pub Date : 2023-09-26 Asim Waqas,Marilyn M Bui,Eric F Glassy,Issam El Naqa,Piotr Borkowski,Andrew A Borkowski,Ghulam Rasool
Digital pathology has transformed the traditional pathology practice of analyzing tissue under a microscope into a computer vision workflow. Whole-slide imaging allows pathologists to view and analyze microscopic images on a computer monitor, enabling computational pathology. By leveraging artificial intelligence (AI) and machine learning (ML), computational pathology has emerged as a promising field
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Deep Learning Can Predict Bevacizumab Therapeutic Effect and Microsatellite Instability Directly from Histology in Epithelial Ovarian Cancer. Lab. Invest. (IF 5.0) Pub Date : 2023-09-22 Ching-Wei Wang,Yu-Ching Lee,Yi-Jia Lin,Nabila Puspita Firdi,Hikam Muzakky,Tzu-Chien Liu,Po-Jen Lai,Chih-Hung Wang,Yu-Chi Wang,Mu-Hsien Yu,Chia-Hua Wu,Tai-Kuang Chao
Epithelial ovarian cancer (EOC) remains a significant cause of mortality among gynecologic cancers, with the majority of cases being diagnosed at an advanced stage. Before targeted therapies were available, EOC treatment relied largely on debulking surgery and platinum-based chemotherapy. Vascular endothelial growth factors have been identified as inducing tumor angiogenesis. According to several clinical
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Quality Management System in Clinical Digital Pathology Operations at a Tertiary Cancer Center. Lab. Invest. (IF 5.0) Pub Date : 2023-09-01 Orly Ardon,Marc Labasin,Maria Friedlander,Allyne Manzo,Lorraine Corsale,Peter Ntiamoah,Jeninne Wright,Kojo Elenitoba-Johnson,Victor E Reuter,Meera R Hameed,Matthew G Hanna
Digital pathology workflows can improve pathology operations by allowing reliable and fast retrieval of digital images, digitally reviewing pathology slides, enabling remote work and telepathology, use of computer-aided tools, and sharing of digital images for research and educational purposes. The need for quality systems is a prerequisite for successful clinical-grade digital pathology adoption and
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Development and Validation of a New BAG-1L-Specific Antibody to Quantify BAG-1L Protein Expression in Advanced Prostate Cancer. Lab. Invest. (IF 5.0) Pub Date : 2023-08-29 Antje Neeb,Ines Figueiredo,Bora Gurel,Daniel Nava Rodrigues,Jan Rekowski,Ruth Riisnaes,Ana Ferreira,Susana Miranda,Mateus Crespo,Daniel Westaby,Maria de Los Dolores Fenor de La Maza,Christina Guo,Juliet Carmichael,Rafael Grochot,Nina Tunariu,Andrew C B Cato,Stephen R Plymate,Johann S de Bono,Adam Sharp
BCL-2-associated athanogene-1L (BAG-1L) is a critical co-regulator that binds to and enhances the transactivation function of the androgen receptor, leading to prostate cancer development and progression. Studies investigating the clinical importance of BAG-1L protein expression in advanced prostate cancer have been limited by the paucity of antibodies that specifically recognize the long isoform.
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Congo Red Staining in Digital Pathology: The Streamlined Pipeline for Amyloid Detection Through Congo Red Fluorescence Digital Analysis. Lab. Invest. (IF 5.0) Pub Date : 2023-08-25 Giorgio Cazzaniga,Maddalena Maria Bolognesi,Matteo Davide Stefania,Francesco Mascadri,Albino Eccher,Federico Alberici,Federica Mescia,Andrew Smith,Filippo Fraggetta,Mattia Rossi,Giovanni Gambaro,Fabio Pagni,Vincenzo L'Imperio
Renal amyloidosis is a rare condition caused by the progressive accumulation of misfolded proteins within glomeruli, vessels, and interstitium, causing functional decline and requiring prompt treatment due to its significant morbidity and mortality. Congo red (CR) stain on renal biopsy samples is the gold standard for diagnosis, but the need for polarized light is limiting the digitization of this
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Single and Multiple High-Risk Human Papillomavirus Infections in Histopathologically Confirmed Cervical Squamous Lesions: Incidences, Distribution, and Associated Detection Rates for Precancerous and Cancerous Lesions. Lab. Invest. (IF 5.0) Pub Date : 2023-08-21 Xiao Tang,Huina Zhang,Tiannan Wang,Wei Jiang,Terri E Jones,Yanmei He,Lei Li,Lingling Tong,Cheng Wang,Wei Wang,Kaixuan Yang,Rutie Yin,Chengquan Zhao
Coinfection with multiple high-risk human papillomavirus (hrHPV) is frequently observed in cervical specimens; however, the clinical significance of concomitant multiple hrHPV infections is poorly understood, and the published results remain inconsistent. A retrospective study at a tertiary care institution was performed, evaluating Tellgenplex human papillomavirus (HPV) 27 genotyping or YanengBio
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Clinical Relevance of Rapid FOXF1-Targeted Sequencing in Patients Suspected of Alveolar Capillary Dysplasia With Misalignment of Pulmonary Veins. Lab. Invest. (IF 5.0) Pub Date : 2023-08-09 Gabriëla G Edel,Janna A Hol,Evelien Slot,Jan H von der Thüsen,Yolande van Bever,Rogier C J de Jonge,Marianne van Tienhoven,Hennie T Brüggenwirth,Annelies de Klein,Robbert J Rottier
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal congenital lung disorder that presents shortly after birth with respiratory failure and therapy-resistant pulmonary hypertension. It is associated with heterozygous point mutations and genomic deletions that involve the FOXF1 gene or its upstream regulatory region. Patients are unresponsive to the intensive treatment
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WITHDRAWN: Engineered knockout of TRPA1 inhibits laser-induced choroidal neovascularization along with associated TGFb1 expression and neutrophil infiltration Lab. Invest. (IF 5.0) Pub Date : 2023-08-09 Yuta Usui,Hiroki Iwanishi,Takayoshi Sumioka,Kana Ichikawa,Masayasu Miyajima,Keiko Usui-Kusumoto,Peter Sol Reinach,Yuka Okada,Shizuya Saika
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Longitudinal Study of Cirrhosis Development in STAM and carbon tetrachloride Mouse Models Using Fourier Transform Infrared Spectral Imaging. Lab. Invest. (IF 5.0) Pub Date : 2023-08-05 Julien Guillard,Valérie Untereiner,Roselyne Garnotel,Camille Boulagnon-Rombi,Cyril Gobinet,Isabelle Proult,Ganesh Dhruvananda Sockalingum,Gérard Thiéfin
Animal models of cirrhosis are of great interest to investigate the pathological process leading to the final stage of cirrhosis. The aim of this study was to analyze the different steps involved in the progressive development of cirrhosis using Fourier transform infrared spectral histology in 2 mouse models of cirrhosis, the STAM model of metabolic cirrhosis, and the carbon tetrachloride-induced cirrhosis
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Arginase 2 Promotes Cisplatin-Induced Acute Kidney Injury by the Inflammatory Response of Macrophages. Lab. Invest. (IF 5.0) Pub Date : 2023-08-02 Yushi Uchida,Kumiko Torisu,Seishi Aihara,Noriyuki Imazu,Hiroaki Ooboshi,Takanari Kitazono,Toshiaki Nakano
Acute kidney injury (AKI) is a complex clinical syndrome with a rapid decrease in renal function caused by several different etiologies, including sepsis, ischemia, and the administration of nephrotoxic drugs. Tubular arginase 2 (ARG2), an arginine-metabolic enzyme, is a potential therapeutic target for AKI, but it has not been confirmed under various AKI conditions. The aim of this study was to investigate
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Role of Stromal Fibroblast-Induced WNT7A Associated with Cancer Cell Migration Through the AKT/CLDN1 Signaling Axis in Oral Squamous Cell Carcinoma. Lab. Invest. (IF 5.0) Pub Date : 2023-08-02 Kou Kayamori,Ken-Ichi Katsube,Hideaki Hirai,Hiroyuki Harada,Tohru Ikeda
Wnt signaling plays a crucial role in the progression of various cancers, including oral squamous cell carcinoma (OSCC). However, the tumor microenvironment (TME) regulating Wnt signaling has not yet been fully elucidated. In this study, we investigated whether cancer-associated fibroblasts (CAFs), the primary components of the TME, activate Wnt signaling and promote tumor progression in OSCC. We conducted
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KLF5/MDM2 Axis Modulates Oxidative Stress and Epithelial-Mesenchymal Transition in Human Lens Epithelial Cells: The Role in Diabetic Cataract. Lab. Invest. (IF 5.0) Pub Date : 2023-07-31 Xiao Li,Doudou Chen,Bowen Ouyang,Shengnan Wang,Yawei Li,Li Li,Siquan Zhu,Guangying Zheng
Diabetic cataract (DC) is a common cause of visual loss in older diabetic subjects. Krüppel-like factor 5 (KLF5) plays an essential role in migration and the epithelial-mesenchymal transition (EMT) in diverse cells and is involved in oxidative stress. However, the effects of KLF5 on DC remain unknown. This study aimed to examine the biological function of KLF5 in DC and its underlying mechanism. The
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Utility of Machine Learning to Detect Cytomegalovirus in Digital Hematoxylin and Eosin-Stained Slides. Lab. Invest. (IF 5.0) Pub Date : 2023-07-30 Corey S Post,Jerome Cheng,Liron Pantanowitz,Maria Westerhoff
Rapid and accurate cytomegalovirus (CMV) identification in immunosuppressed or immunocompromised patients presenting with diarrhea is essential for therapeutic management. Due to viral latency, however, the gold standard for CMV diagnosis remains to identify viral cytopathic inclusions on routine hematoxylin and eosin (H&E)-stained tissue sections. Therefore, biopsies may be taken and "rushed" for
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Quantitative Assessment of Hepatic Steatosis Using Label-Free Multiphoton Imaging and Customized Image Processing Program. Lab. Invest. (IF 5.0) Pub Date : 2023-07-28 Xingxin Huang,Yuan-E Lian,Lida Qiu,XunBin Yu,Jikui Miao,Shichao Zhang,Zheng Zhang,Xiong Zhang,Jianxin Chen,Yannan Bai,Lianhuang Li
Nonalcoholic fatty liver disease is rapidly becoming one of the most common causes of chronic liver disease worldwide and is the leading cause of liver-related morbidity and mortality. A quantitative assessment of the degree of steatosis would be more advantageous for diagnostic evaluation and exploring the patterns of disease progression. Here, multiphoton microscopy, based on the second harmonic
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Formalin Fixation Followed by Paraffin Embedding Allows Long-Term Storage of Proteins for Liquid Chromatography-Tandem Mass Spectrometry Analysis. Lab. Invest. (IF 5.0) Pub Date : 2023-07-28 Andrei Feldiorean,James Bena,Megan O Nakashima,Adam J McShane,Claudiu V Cotta
In an anatomical pathology laboratory, liquid chromatography-tandem mass spectrometry (LC-MS/MS) is used to characterize amyloid deposits identified in formalin-fixed paraffin-embedded tissue (FFPET). However, the development of additional tests is partially limited by the lack of information the passage of time has on the proteins in FFPET. To investigate the reliability of LC-MS/MS in the analysis
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Identification of Proteomic Biomarkers in Proliferative Verrucous Leukoplakia through Liquid Chromatography With Tandem Mass Spectrometry. Lab. Invest. (IF 5.0) Pub Date : 2023-07-26 Esteban Arroyo,Mario Pérez Sayáns,Susana Belen Bravo,Camila de Oliveira Barbeiro,Mariana Paravani Palaçon,Cintia M Chamorro Petronacci,María García Vence,María Del Pilar Chantada Vázquez,Andrés Blanco Carrión,José M Suárez Peñaranda,Abel García García,Pilar Gándara Vila,Janete Días Almeida,Giovani Carlo Veríssimo da Costa,Fábio César Sousa Nogueira,Joseph Albert Medeiros Evaristo,Denise de Abreu Pereira
Proliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder associated with high risk of malignant transformation. Currently, there is no treatment available, and restrictive follow-up of patients is crucial for a better prognosis. Oral leukoplakia (OL) shares some clinical and microscopic features with PVL but exhibits different clinical manifestations and a lower rate of malignant
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Genome Doubling Shapes High-Grade Transformation and Novel EWSR1::LARP4 Fusion Shows SOX10 Immunostaining in Hyalinizing Clear Cell Carcinoma of Salivary Gland. Lab. Invest. (IF 5.0) Pub Date : 2023-07-20 Kenya Kobayashi,Masahito Kawazu,Seiichi Yoshimoto,Toshihide Ueno,Go Omura,Yuki Saito,Mizuo Ando,Eigitsu Ryo,Airi Sakyo,Akihiko Yoshida,Yasushi Yatabe,Hiroyuki Mano,Taisuke Mori
Hyalinizing clear cell carcinoma (HCCC) is a rare indolent malignant tumor of minor salivary gland origin with EWSR1::ATF1 rearrangement. Pathologically, the tumor cells possess a clear cytoplasm in a background of hyalinized stroma. Generally, the tumor cells are positive for p63 and p40 and negative for s100 and α-smooth muscle actin, suggesting that they differentiate into squamous epithelium and
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PD-L1 Expression is Linked to Tumor-Infiltrating T-Cell Exhaustion and Adverse Pathological Behavior in Pheochromocytoma/Paraganglioma. Lab. Invest. (IF 5.0) Pub Date : 2023-07-04 Anze Yu,Xiaowen Xu,Yingxian Pang,Minghao Li,Junhang Luo,Jing Wang,Longfei Liu
Pheochromocytoma/paraganglioma (PPGL) is an endocrine-related tumor associated with excessive catecholamine release and has limited treatment options once metastasis occurs. Although recent phase 2 clinical trials of immune checkpoint inhibitors in the treatment of PPGL have preliminarily shown promising results, the fundamentals of immunotherapy for PPGL have not yet been established. In the early
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Effect of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition on Podocytes in Mouse Nephrotic Syndrome. Lab. Invest. (IF 5.0) Pub Date : 2023-06-16 Taihei Suzuki,Masayuki Iyoda,Nobuhiro Kanazawa,Shohei Tachibana,Hirokazu Honda
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is known to play a crucial role in dyslipidemia, and an increase in serum PCSK9 levels has also been reported in patients with nephrotic syndrome (NS). However, the specific effects of PCSK9 in kidney disease and the therapeutic potential of targeting PCSK9 in NS remain elusive. We thus investigated the effects of evolocumab (EVO) in mice with adriamycin